This proposal is for the purchase of an analytical ultracentrifuge (Beckman Coulter model XL-I). This instrument will provide the capability for state-of-the-art characterization of macromolecular behavior under solution conditions, which can reveal information about macromolecular conformation, interactions with large and small molecules, self-association and sample heterogeneity. Since these biophysical properties determine many aspects of the function, inhibition and/or regulation of biological systems, the ability to study these properties will significantly enhance the impact and breadth of a large number of NIH-funded research programs at Ohio State University. As there is currently no analytical ultracentrifuge at Ohio State, this purchase will enable biomedically relevant studies that are currently not possible due to limited access and high cost of off-site fee-for-service facilities. Many experiments require extensive optimization of sample preparation, buffer conditions, run times, etc., which is not feasible to do off-site due to time constraints and expense. Having an on-site instrument will have a major impact on the investigation of aminoacyl-tRNA synthetase editing complexes, viral-host cell interactions critical for HIV infection, diseases caused by protein destabilization, the molecular basis of gene regulation, the role of histone modifications, and on studies of human DNA polymerases.